In the August 8 online edition of Science, researchers representing the National Institute of Allergy and Infectious Diseases (NIAID) reported the results of a Phase I clinical trial in which more than 50 adults were intravenously immunized with a malaria vaccine made of whole Plasmodium falciparum (Pf) sporozoites. The study’s authors include Robert A. Seder, M.D., chief of cellular immunology at the NIAID’s Vaccine Research Center.

To date, the only way to achieve long-lasting protection against malaria has been to allow human subjects to suffer bites from mosquitos carrying Pf sporozoites—the cells that develop in the Anopheles mosquito’s salivary glands. In response to these bites, human subjects may boost their immunity.

For as long as the efficacy of allowing mosquitoes to bite humans has been known—about 40 years—the deficiencies of this approach have been known, too. Malaria remains one of mankind’s greatest scourges. In 2010, according to the World Health Organization, there were 216 million episodes of malaria and 655,000 deaths worldwide. Of these deaths, around 91% occurred in the African region, followed by the Southeast Asian region (6%) and the Eastern Mediterranean region (3%). About 86% of deaths globally were among children.

New Research Shows Promise

Despite the pressing need for better protection against malaria, parasites sufficiently weak for an injectable vaccine but still alive and metabolically active could not be manufactured. But current research shows promise. For example, in the Science report, Dr. Seder and his colleagues describe how they developed a PfSPZ vaccine composed of attenuated, aseptic, purified, and cryopreserved Pf sporozoites. According to the authors, PfSPZ was safe and well tolerated when intravenously administered 4–6 times to 40 adults.

For their immunization trial, Dr. Seder and his colleagues intravenously immunized study participants over the course of a year. Some individuals received four doses of the vaccine; others received five. Just a third of the former group developed malaria, while none of the latter group did. The greater the number of doses, the more sporozoite-specific antibodies the researchers observed in the subjects’ blood. T cells also responded to the vaccine’s weakened sporozoites in a dose-dependent manner, and the vaccine was well tolerated by the subjects.

The Intravenous Route

The investigators said that currently two clinical trials of the PfSPZ vaccine have established that its intravenous administration induced superior immunogenicity and protective efficacy compared to subcutaneous and intradermal administration. These findings are consistent with prior studies in nonhuman primates showing that intravenous administration induced a higher frequency of liver-resident CD8+ T cells specific for PfSPZ and antibodies against PfSPZ.

The investigators note that while the intravenous route is routinely used for therapeutic interventions in humans, it has not previously been used for administration of a preventive infectious disease vaccine. A series of clinical trials of the PfSPZ vaccine administered by intravenous injection are now planned in Africa, Europe, and the United States to expand critical data on the vaccine for clinical development as a method to prevent malaria in other high-risk groups and for mass immunization of populations to eliminate Pf malaria from geographically defined areas. It remains to be seen, they noted, whether an intravenous vaccine can be delivered in a widespread manner to the populations most in need.

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